Nilotinib is chemically, 4-methyl-N-[3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl]-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]-benzamide and has the structural formula:

Nilotinib is a tyrosine kinase inhibitor used for the treatment of drug-resistant chronic myelogenous leukemia (CML), and in particular, for the treatment of chronic phase and accelerated phase Philadelphia chromosome positive chronic myeloid leukemia (CML) in adult patients whose disease has progressed on or who cannot tolerate other therapies that included imatinib. Nilotinib is administrated as a hydrochloride salt in forms of capsules that are marketed in the USA and the EU under the name Tasigna®.
Polymorphism is defined as “the ability of a substance to exist as two or more crystalline phases that have different arrangement and/or conformations of the molecules in the crystal Lattice. Thus, in the strict sense, polymorphs are different crystalline forms of the same pure substance in which the molecules have different arrangements and/or different configurations of the molecules”. Different polymorphs may differ in their physical properties such as melting point, solubility, X-ray diffraction patterns, etc. Although those differences disappear once the compound is dissolved, they can appreciably influence pharmaceutically relevant properties of the solid form, such as handling properties, dissolution rate and stability. Such properties can significantly influence the processing, shelf life, and commercial acceptance of a polymorph. It is therefore important to investigate all solid forms of a drug, including all polymorphic forms, and to determine the stability, dissolution and flow properties of each polymorphic form. Polymorphic forms of a compound can be distinguished in the laboratory by analytical methods such as X-ray diffraction (XRD), Differential Scanning calorimetry (DSC) and Infrared spectrometry (IR).
Solvent medium and mode of crystallization play very important role in obtaining a crystalline form over the other.
Nilotinib and its hydrochloride salt can exist in different polymorphic forms, which may differ from each other in terms of stability, physical properties, spectral data and methods of preparation.
Nilotinib hydrochloride and its salts were disclosed in U.S. Pat. No. 7,169,791.
PCT publication no. WO 2007/015870 ('870 patent) disclosed crystalline form A, form A′, form A″, form B, form B′, form SB, form SB′, form C, form SC, form D, form SE and amorphous form of nilotinib hydrochloride.
According to the '870 patent, crystalline form A of nilotinib hydrochloride was characterized by an X-ray powder diffraction pattern having peaks expressed as 2θ at about 8.5, 11.0, 11.5, 18.8, 19.2, 20.8, 22.1 and 26.0 degrees.
PCT publication no. WO 2010/054056 ('056 patent) disclosed crystalline form T1, form T2, form T3, form T4, form T5, form T6, form T7, form T8, form T9, form T10, form T11, form T12, form T13, form T14, form T15, form T16, form T17, form T18 and form T19 of nilotinib hydrochloride.
According to the '056 patent, crystalline form T2 of nilotinib hydrochloride was characterized by an X-ray powder diffraction pattern having peaks expressed as 2θ at about 7.1, 8.7, 11.5, 14.0, 15.3, 16.6, 17.4, 19.4 and 25.5±0.2 degrees.
According to the '056 patent, crystalline form T3 of nilotinib hydrochloride was characterized by an X-ray powder diffraction pattern having peaks expressed as 2θ at about 7.0, 8.5, 11.4, 12.1, 14.2, 17.2, 19.2, 22.1, 23.2 and 25.2±0.2 degrees.
According to the '056 patent, crystalline form T11 of nilotinib hydrochloride was characterized by an X-ray powder diffraction pattern having peaks expressed as 2θ at about 7.4, 8.7, 17.4, 25.3, 26.2 and 35.1±0.2 degrees.
According to the '056 patent, crystalline form T13 of nilotinib hydrochloride was characterized by an X-ray powder diffraction pattern having peaks expressed as 2θ at about 8.2, 12.8, 15.7, 16.5, 21.7 and 23.9±0.2 degrees.
We have discovered novel crystalline form of nilotinib hydrochloride. The novel form has been found to be stable over the time and reproducible and so, suitable for pharmaceutical preparations.
Thus, an object of the present invention is to provide a novel crystalline form of nilotinib hydrochloride, process for its preparation and pharmaceutical compositions comprising it.